title: The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection.
abstract: Human semen contains peptides capable of forming amyloid fibrils termed semen-derived enhancer of viral infection (SEVI) that can greatly increase human immunodeficiency virus (HIV) infection. While SEVI appears to enhance virion attachment to target cells, its underlying mechanism of action is unknown. We now demonstrate that the intrinsic positive charges of SEVI (pI = 10.21) facilitate virion attachment to and fusion with target cells. A mutant form of SEVI in which lysines and arginines are replaced with alanines retains the ability to form amyloid fibrils but is defective in binding virions and enhancing infection. In addition, the interaction of wild-type SEVI with virions and the ability of these fibrils to increase infection are abrogated in the presence of various polyanionic compounds. These anionic polymers also decrease the enhancement of HIV infection mediated by semen. These findings suggest that SEVI enhances viral infection by serving as a polycationic bridge that neutralizes the negative charge repulsion that exists between HIV virions and target cells. Combinations of agents that neutrale SEVI action and produce HIV virucidal effects are an attractive future direction for microbicide development.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, P.O. Box 419100, San Francisco, CA 94141-9100, USA.
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Roan
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arhel
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
authors.forename: Jason
authors.initials: J
authors.lastname: Neidleman
authors.forename: Akiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Karen
authors.initials: K
authors.lastname: Smith-McCune
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: Warner C
authors.initials: WC
authors.lastname: Greene
mesh_terms: D019943:Amino Acid Substitution; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D007526:Isoelectric Point; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012661:Semen / Q000737:chemistry* / Q000821:virology*; D053585:Virus Attachment
chemical_list: D050505:Mutant Proteins; D010455:Peptides